Sickle cell anemia is the result of the replacement of a glutamic acid at position 6 with a valine. This is the result of the point of mutation of A yields T. Although prenatal diagnosis of sickle cell anemia by fetal blood sampling is feasible, the ultimate acceptibility of the procedure depends on the overall risk of blood sampling. Thus alternative methods of prenatal diagnosis will have to be devised. These could include the development of safer methods for fetal blood sampling or the use of the methods which do not require fetal blood. The goal of this research is to synthesize oligodeoxyribonucleotides of defined sequence for the analysis of point mutation in a mammalian aenome (sickle cell anemia) by applying very stringent nucleic acid hybridization criteria. The specific goals are: 1) To synthesize two 17 nucleotide long oligomers complementary to both strands of rabbit B-globin gene in the region coding for amino acids 5-9. In addition, two 17 long oligomers will be synthesized which are complementary to the same region but which have one base change (A yields T in one stran, T yields A in the other) as a model probe for point mutation. Hybridizations will be carried out with the cloned rabbit B-globin gene and whole chromosomal DNA to find conditions where the mismatched oligonucleotides will not hybridize while the non-mismatched will. 2) To synthesize 17-long oligonucleotides complementary to human Bea-globin gene at the region coding for amino acids 5-9. One pair of oligomers will be synthesized complementary to normal human globin gene and one pair complementary to sickle cell globin genes. These oligomers will be hybridized to DNA from normal or sickle cell fibroblasts under the conditions established in 1). The pattern of hybridization, that is hybridization with normal probes, with sickle cell probes, or with both, will identify normal, sickle cell, or heterozygous individuals.